Research Affiliates

Eduardo Butelman, Ph.D.

Dr. Butelman is interested in quantitatively defining the in vivo effects of neuropeptides and synthetic ligands at the κ opioid receptor system. The κ system is thought to be involved in several neuropsychiatric functions, including anxiety, depression and responsiveness to drugs of abuse, and in particular propensity to relapse. His aim is to open the door for the development of new pharmacotherapeutic treatments for opiate and cocaine addiction based on a better understanding of their etiology.

Dr. Butelman’s earlier work focused on quantifying in vivo effects of the neuropeptide dynorphin — an unstable compound that acts at the κ opioid receptor. Using the hormone prolactin as a biomarker for κ-receptor activation, Dr. Butelman defined the in vivo pharmacological potency and efficacy of this endogenous agonist at the κ opioid receptor system.

More recently, Dr. Butelman has focused on characterizing the basic pharmacology of salvinorin A, a powerful hallucinogenic compound from the plant Salvia divinorum. In 2004, Dr. Butelman and his colleagues were the first to confirm in vivo that salvinorin A is a κ-receptor agonist. Dr. Butelman also showed that salvinorin A, like dynorphin, increases prolactin levels, which could then be used as biomarkers for salvinorin A activity at κ opioid receptors. In a drug discrimination paradigm, Dr. Butelman showed that subjects did not differentiate the subjective-like effects of salvinorin A from those of a known synthetic κ-agonist. He further showed that a κ-receptor antagonist treatment administered before salvinorin A could both prevent and reverse behavioral effects of salvinorin A. Furthermore, a classic serotonergic hallucinogen did not share the interoceptive effects of salvinorin A. Overall, these findings indicate that the behavioral effects of salvinorin A are thus completely separate from known “classic” hallucinogens and further implicates the κ system as a powerful mechanism underlying higher perceptual functions.